Abstract
The epithelial-mesenchymal transition (EMT) is a complex transformation process that induces local and distant progression of many malignant tumours. Due to its complex array of proteins that are dynamically over-/underexpressed during this process, proteomic technologies gained their place in the EMT research in the last years. Proteomics has identified new molecular pathways of this process and brought important insights to develop new therapy targets. Various proteomic tools and multiple combinations were developed in this area. Out of the proteomic technology armentarium, mass spectrometry and array technologies are the most used approaches. The main characteristics of the proteomic technology used in this domain are high throughput and detection of minute concentration in small samples. We present herein, using various proteomic technologies, the identification in cancer cell lines and in tumour tissue EMT-related proteins, proteins that are involved in the activation of different cellular pathways. Proteomics has brought besides standard EMT markers (e.g., cell-cell adhesion proteins and transcription factors) other future potential markers for improving diagnosis, monitoring evolution, and developing new therapy targets. Future will increase the proteomic role in clinical investigation and validation of EMT-related biomarkers.
Highlights
The epithelial-to-mesenchymal transition (EMT) process allows the cellular differentiation from polarized epithelial phenotype to mesenchymal characteristics
By ChIP-seq, it was identified that UHRF2 and EMT-transcription factors (TFs) share the same genomic binding motifs, and the interactome analysis highlights that UHRF2 interact with TFs (e.g., TCF7L2), proteins involved in chromatin remodelling and histone alterations, data confirmed by immunoprecipitation combined with MS
In PC-3 and DU-145 prostate cancer cell lines using several proteomic technologies, EMT-related proteins were investigated upon caffeic acid phenethyl ester (CAPE) treatment, and it was shown that MMP-9 and MMP-2 have reduced activities
Summary
The epithelial-to-mesenchymal transition (EMT) process allows the cellular differentiation from polarized epithelial phenotype to mesenchymal characteristics. Markers, the expression of fibroblast-specific protein 1 (FSP1), vimentin, α-smooth muscle actin (α-SMA) correlated with low expression or loss of cytokeratins, mucin-1, occludin, and desmoplakin is an indicator of cells undergoing EMT [6] Another cytoskeletal marker, β-catenin, can be a marker of either epithelial normal cells or mesenchymal cells, depending on its cell localization [5]. Multiple reaction monitoring was introduced using triple quad MS technology and/or several tribrid high-resolution MS The evolution of these new types of MS was a consequence of the clinical proteomic needs seeking to measure detailed proteomic panels further to be used in early detection, disease and/or therapy monitoring, patient stratification, and so on [11]. An intricate process like ETM would beneficiate from the latest proteomic approaches to study the dynamics of this complex process
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